A Study of Elacytarabine (CP-4055) Plus Idarubicin as Second Course Remission-Induction Therapy in Patients With Acute Myeloid Leukaemia

Elacytarabine (CP-4055) is a pro-drug of ara-C currently used in the treatment of patients
with acute myeloid leukaemia. Patients with nucleoside transporter deficiency (hENT1) seem
to have less benefit from cytarabine compared to those with a high expression of the
transporter. Preclinical studies indicate that elacytarabine is independent of this
transporter. Therefore, patients with low expression of hENT1 and treated with elacytarabine
are anticipated to have a better outcome compared to patients treated with ara-C. The main
objective of this study is to assess the biological activity of elacytarabine in combination
with idarubicin in patients with acute myeloid leukaemia. In addition, the correlation
between hENT1 (human equilibrative nucleoside transporter 1) and overall survival will be
studied. Patients will be treated with elacytarabine plus idarubicin independent of their
hENT1 status. Determination of the patients' hENT1 expression level will be done
retrospectively. This study will also explore the safety profile of elacytarabine in
combination with idarubicin.

Inclusion Criteria:

1. Patients with a confirmed diagnosis of AML according to WHO classification (excluding
acute promyelocytic leukaemia)

2. Patients who have received one previous standard dose ara-C-containing regimen aiming
at induction of complete remission (CR) and who have more than 5 % remaining blast
cells in bone marrow following the first course of remission-induction or by other
means documented residual disease (i.e. circulating blasts, persistent chloromas,
other evident disease from day 12 on).

3. Patients from whom samples for determination of hENT1 status on leukemic blast cells
can be taken and prepared at diagnosis and/or at baseline

4. Patients must be 18 years of age or older

5. Patients must have ECOG performance status (PS) of 0 - 2

6. Left ventricular ejection fraction (LVEF) must be >= 45 % as measured by MUGA scan or
2D ECHO within 14 days prior to start of therapy.

7. Women of child-bearing potential (i.e., women who are pre-menopausal or not
surgically sterile) must have a negative serum or urine pregnancy test within 2 weeks
prior to beginning treatment on this study

8. Male and female patients must use acceptable contraceptive methods for the duration
of time on study, and males also for 3 months after the last elacytarabine dose

9. Patients must be capable of understanding and complying with parameters as outlined
in the protocol, and able and willing to sign a written informed consent form

10. Patients must have the following clinical laboratory values:

- Serum creatinine <= 1.5 x the institutional upper limit of normal (ULN)

- Total bilirubin <= 1.5 x the ULN according to national prescribing information
unless considered due to Gilbert's syndrome

- Alanine aminotransferase (ALT) (SGPT), or aspartate aminotransferase (AST)
(SGOT) <= 2.5 x the ULN unless considered due to organ leukemic involvement

11. Patients must be eligible for administration of idarubicin according to current
national prescribing information for idarubicin

Exclusion Criteria:

1. A history of allergic reactions to egg, idarubicin and/or other anthracyclines or
other components of the products. A history of allergic reactions to ara-C of CTCAE
grade 3 or 4

2. Persistent clinically significant and relevant toxicities from the previous course of
chemotherapy

3. A cancer history, that according to the investigator might confound the assessment of
the study endpoints

4. Patients with prior treatment with a cumulative dose of doxorubicin or equivalent
exceeding 300 mg/m2 according to the following calculation index: X/300 + Y/160 < 1
where X is the doxorubicin or equivalent dose in mg/m2 and Y is the mitoxantrone dose
in mg/m2. These calculations are to be used as guidance as there is no maximum
cumulative dose defined in the summary of product characteristics (SPC) for
idarubicin. The patient should tolerate minimum one course of combination therapy

5. Active heart disease including myocardial infarction within the previous 3 months,
symptomatic coronary disease, arrhythmias not controlled by medication, or
uncontrolled congestive heart failure. Any NYHA grade 3 or 4

6. Known positive status for human immunodeficiency virus (HIV)

7. Pregnant and nursing patients are excluded because the effects of elacytarabine on a
fetus or a nursing child are unknown

8. Uncontrolled intercurrent illness including, but not limited to uncontrolled
infection, or psychiatric illness/social situations that may reduce compliance with
study requirements

9. Patients receiving hydroxyurea within the last 12 hours prior to treatment on this
protocol or any other investigational or standard cytotoxic treatment within the
last 14 days, except the first remission-induction course

10. Any medical condition, which in the opinion of the investigator places the patient at
an unacceptably high risk for toxicities